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To assess the safety of oral therapy with ZD6474 by evaluating the frequency, severity, and duration of treatment-emergent adverse events in patients with poor prognosis lung cancer.

To record the extent, frequency and duration of any tumor responses to this treatment regimen and assess whether ZD6474 augments the efficacy of radiation therapy in non-small cell lung cancer patients.

To determine the recommended phase II dose of ZD6474 for future clinical studies with radiation therapy.

ZD6474 is a new drug that is thought to block the formation of new blood vessels. The growth of new blood vessels is called angiogenesis. Angiogenesis is thought to be essential for the growth of tumors beyond a small size.

Before treatment starts, you will have several tests and procedures performed. These tests will include a complete medical history and physical exam, including recent weight loss, vital signs, and a test to check how easily you swallow. Laboratory tests needed will require a urine sample, and blood samples (about 3-4 teaspoons). Women who are able to have children must have a negative blood pregnancy test in order to participate in this study. You will have an electrocardiogram (ECG--a test to measure the electrical activity of the heart), heart function tests, and scans of your brain, chest, and bones. You will also have PET scans performed.

You may take part in this study if you are a patient with NSCLC who is not able to receive chemotherapy.

If you are eligible to participate, you will receive ZD6474 by mouth once a day every day, along with radiation therapy. You must take your medication on an empty stomach, at approximately the same time each morning. ZD6474 should be swallowed as a whole tablet (not chewed, crushed or divided) and taken with 8 oz of water. Missed doses may be taken by the end of the same calendar day. However, if a subject misses taking their scheduled dose on the same day, he or she must take the next scheduled dose and the missed dose will not be made up. The missed dose must be documented on patients medication diary ZD6474 will be given 5-7 days before starting radiation therapy and will continue through the entire course of radiation therapy, unless there is proof that the cancer is progressing. ZD6474 may interact with many commonly prescribed medications. A list will be provided to you.

Radiation will be given every weekday (Monday - Friday) for 3-7 weeks as your doctor thinks is necessary and useful. You will have weekly evaluations during radiation treatment, including blood samples (3-4 teaspoons) for routine testing, oxygen saturation (a test that measures how much oxygen is in the blood), and physical examination.

If you need anti-nausea medication (such as Zofran) during this study, you will have an ECG performed within 24 hours of starting the medication and then again at least once a week while you remain on the medication.

You will continue on study, unless there is evidence that the disease has gotten worse or intolerable side effects occur.

You will be seen for a follow-up visit one month after completing radiation therapy, and again at 3 months. You will then come in for a follow-up visit every 3 months for 2 years, then every 6 months for 3 years, then once a year. Scheduled tests and follow-ups should be performed within 1 week (before or after) of the scheduled time period (a 14-day window). At these visits, you will have blood draws (about 3-4 teaspoons), urine tests and x-rays. You will have an ECG, lung function tests, and PET/CT scans.

Participants who are blood donors should not donate blood during the study and for 3 months following their last dose of study treatment.

This is an investigational study. ZD6474 is not FDA approved, and has been authorized for research only. A total of up to 48 patients will take part in this study. All patients will be enrolled at UT MD Anderson Cancer Center (MDACC).

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

international normalized ratio (INR) within normal laboratory value range and prothrombin time (PT) and partial thromboplastin time (PTT) within 3 seconds of normal range.

Potassium must be within normal laboratory value range. Serum calcium and magnesium must be within normal range. Supplementation may be used to normalize.

Patients with distant metastases and life expectancy greater than or equal to 3 months are eligible.

Due to the experimental nature of ZD6474, female patients must be one year post-menopausal, surgically sterile, or using an acceptable method of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation.) Male patients must be surgically sterile or using an acceptable method of contraception during their participation in this study.

A negative pregnancy test within 72 hours prior to administration of ZD6474 will be required for women of childbearing potential.

Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of M.D. Anderson Cancer Center. Patients must also agree to study restrictions and return for required assessments. The only approved consent form is attached to this protocol.

Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >/=2 (see Appendix J) within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.

QTc with Bazett's correction that is unmeasurable, or >/= 480 msec on screening Electrocardiograph (ECG/EKG). If a patient has QTc >/= 480 msec on screening EKG, the screening EKG may be repeated twice (at least 24 hours apart). The average QTc from the three screening EKGs must be <480 msec in order for the patient to be eligible for the study.

Patients cannot have a history of QT prolongation with other medication

Patients cannot have a congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.

Any concomitant medications that affect QTc or induce Torsades de Pointes and cannot be discontinued

Patients cannot have a severe hypersensitivity reaction to drugs formulated with polysorbate 80

Patients cannot have any evidence of severe or uncontrolled systemic disease, including known Hepatitis B or HIV infection. Screening for chronic conditions is not required, although subjects known to have such conditions should not be enrolled.

Patient cannot have had any active cancer in addition to their current lung cancer within the last 3 years with the exception of superficial skin cancer (e.g., basal cell or squamous cell carcinoma)

Patient cannot have any central nervous system (CNS) metastases, unless treated at least 4 weeks before entry, and stable without steroid treatment for 1 week